The metabolic response to endotoxemia closely mimics those seen in sepsis.Here, we show that the urinary excretion of the metabolite 2-hydroxyglutarate (2HG) is dramatically suppressed following lipopolysaccharide (LPS) administration in vivo, and in human septic patients.We further show that enhanced Cologne activation of the enzymes responsible for 2-HG degradation, D- and L-2-HGDH, underlie this effect.To determine the role of supplementation with 2HG, we carried out co-administration of LPS and 2HG.
This co-administration Elevation Can in mice modulates a number of aspects of physiological responses to LPS, and in particular, protects against LPS-induced hypothermia.Our results identify a novel role for 2HG in endotoxemia pathophysiology, and suggest that this metabolite may be a critical diagnostic and therapeutic target for sepsis.